HIV-1 gp160 as a Modifier of Th1 and Th2 Cytokine Response: Gp160 Suppresses Interferon-γ and Interleukin-2 Production Concomitantly with Enhanced Interleukin-4 Production in Vitro

Disease progression in HIV-1 infection is reported to be associated with a gradual shift in CD4⁺ T cell function from a Th type 1 to a Th type 2 of response, but the underlying mechanism remains unclear. In this study, the effect of HIV-1 envelope glycoprotein gp160 on secretion of cytokines IFN-γ/IL-2 (Th1 type) and IL-4 (Th2 type) was analyzed using freshly isolated unfractioned peripheral blood mononuclear cells (PBMC), CD4⁺ T cell lines, and PBMC depleted of CD8⁺ cells (CD8^- PBMC) as target cells. Pretreatment of these cells with HIV gp160 significantly reduced PHA-induced secretion of IFN-γ and IL-2 but augmented IL-4 production. This effect of gp160 was not observed when the target cells consisted of PBMC depleted of either CD4⁺ cells (CD4^- PBMC) or of CD2⁺ cells (CD2^- PBMC). Pretreatment of gp160 with soluble CD4-immunoglobulin chimeric molecules abrogated the observed effects of gp160, suggesting that CD4-gp120 interaction is required for modification of the cytokine secretion profile. Our results suggest that exposure of CD4⁺ T cells to HIV-1 envelope proteins may modify the responses evoked by additional stimuli in favor of a Th2-type dominant response.